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Fluconazole loading dose pharmacokinetics and safety in infants.

Publication ,  Journal Article
Piper, L; Smith, PB; Hornik, CP; Cheifetz, IM; Barrett, JS; Moorthy, G; Hope, WW; Wade, KC; Cohen-Wolkowiez, M; Benjamin, DK
Published in: Pediatr Infect Dis J
May 2011

BACKGROUND: Invasive candidiasis is a leading cause of morbidity and mortality in critically ill infants. Prompt administration of fluconazole and achievement of the therapeutic target (area under the curve 0 to 24 hours >400 mg*h/L) improve outcomes in candidemic patients. A loading dose of fluconazole is advised for older patients but has not been evaluated in infants. We sought to determine the pharmacokinetics and safety of a fluconazole loading dose in infants at risk for invasive fungal infection. METHODS: We enrolled 10 hospitalized infants <60 days old with suspected systemic fungal infection in this open-label study; 9 received a 25-mg/kg fluconazole loading dose followed by a maintenance dose of 12 mg/kg every 24 hours for 4 additional days. Plasma samples were obtained following the loading and steady-state doses (doses 3-5). We used a 1-compartment model to fit the data to estimate pharmacokinetic indices. RESULTS: Data from 57 drug concentrations obtained from 8 infants (median postnatal age, 16 days [interquartile range, 13-32] and median gestational age, 37 weeks [35-38]) showed that the median fluconazole area under the curve 0 to 24 hours (mg*h/L) in this population was 479 (347-496). Of the 8 infants who received the loading dose, 5 (63%) achieved the therapeutic target on the first day of dosing, and all infants achieved a fluconazole 24-hour trough concentration >8 μg/mL. No adverse events were thought to be related to fluconazole therapy. CONCLUSIONS: A loading dose of fluconazole (25 mg/kg) was safe in this small cohort of young infants and achieved the therapeutic target more rapidly than traditional dosing.

Duke Scholars

Published In

Pediatr Infect Dis J

DOI

EISSN

1532-0987

Publication Date

May 2011

Volume

30

Issue

5

Start / End Page

375 / 378

Location

United States

Related Subject Headings

  • Tandem Mass Spectrometry
  • Plasma
  • Pediatrics
  • Infant, Newborn
  • Infant
  • Humans
  • Fluconazole
  • Chromatography, Liquid
  • Candidiasis
  • Antifungal Agents
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Piper, L., Smith, P. B., Hornik, C. P., Cheifetz, I. M., Barrett, J. S., Moorthy, G., … Benjamin, D. K. (2011). Fluconazole loading dose pharmacokinetics and safety in infants. Pediatr Infect Dis J, 30(5), 375–378. https://doi.org/10.1097/INF.0b013e318202cbb3
Piper, Lauren, P Brian Smith, Christoph P. Hornik, Ira M. Cheifetz, Jeffrey S. Barrett, Ganesh Moorthy, William W. Hope, Kelly C. Wade, Michael Cohen-Wolkowiez, and Daniel K. Benjamin. “Fluconazole loading dose pharmacokinetics and safety in infants.Pediatr Infect Dis J 30, no. 5 (May 2011): 375–78. https://doi.org/10.1097/INF.0b013e318202cbb3.
Piper L, Smith PB, Hornik CP, Cheifetz IM, Barrett JS, Moorthy G, et al. Fluconazole loading dose pharmacokinetics and safety in infants. Pediatr Infect Dis J. 2011 May;30(5):375–8.
Piper, Lauren, et al. “Fluconazole loading dose pharmacokinetics and safety in infants.Pediatr Infect Dis J, vol. 30, no. 5, May 2011, pp. 375–78. Pubmed, doi:10.1097/INF.0b013e318202cbb3.
Piper L, Smith PB, Hornik CP, Cheifetz IM, Barrett JS, Moorthy G, Hope WW, Wade KC, Cohen-Wolkowiez M, Benjamin DK. Fluconazole loading dose pharmacokinetics and safety in infants. Pediatr Infect Dis J. 2011 May;30(5):375–378.

Published In

Pediatr Infect Dis J

DOI

EISSN

1532-0987

Publication Date

May 2011

Volume

30

Issue

5

Start / End Page

375 / 378

Location

United States

Related Subject Headings

  • Tandem Mass Spectrometry
  • Plasma
  • Pediatrics
  • Infant, Newborn
  • Infant
  • Humans
  • Fluconazole
  • Chromatography, Liquid
  • Candidiasis
  • Antifungal Agents